title: Association of systolic blood pressure with mortality in patients with heart failure with reduced ejection fraction: a complex relationship.
abstract: BACKGROUND
  In ambulatory patients with heart failure with reduced ejection fraction (HFrEF), high systolic blood pressure (SBP) is associated with better outcomes. However, it is not known whether there is a ceiling beyond which high SBP has a detrimental effect. Thus, our aim was to assess the linearity of association between SBP and mortality.
  
  
  METHODS
  We used the External Peer Review Program (EPRP) and Digitalis Investigation Group (DIG) trial databases of HFrEF patients. Linearity of association of SBP with mortality was assessed by plotting Martingale residuals against SBP. To assess the patterns of relationship of SBP with mortality, we used restricted cubic spline analysis with Cox proportional hazards model.
  
  
  RESULTS
  In patients with mild-to-moderate left ventricular systolic dysfunction (LVSD) (30% ≤ LVEF < 50%), SBP had a nonlinear association with mortality in both EPRP (n = 3,693) and DIG (n = 3,263) databases. In these patients, SBP had a significant U-shaped association with mortality in EPRP and a trend toward U-shaped relationship in DIG database. In patients with severe LVSD (LVEF <30%), SBP had a linear association with mortality in both EPRP (n = 2,906) and DIG (n = 3,537) databases, with lower SBP being associated with increased mortality.
  
  
  CONCLUSIONS
  Systolic blood pressure has a complex nonlinear association with mortality in patients with heart failure. Whereas it has a U-shaped association in patients with mild-to-moderate LVSD, it has a linear association with mortality in patients with severe LVSD. Recognition of this pattern of association of blood pressure profile may help clinicians in providing better care for their patients and help improve existing prediction models.
authors.affiliation: Baylor College of Medicine, Houston, TX, USA.
authors.forename: Sameer
authors.initials: S
authors.lastname: Ather
authors.forename: Wenyaw
authors.initials: W
authors.lastname: Chan
authors.forename: Annirudha
authors.initials: A
authors.lastname: Chillar
authors.forename: David
authors.initials: D
authors.lastname: Aguilar
authors.forename: Allison M
authors.initials: AM
authors.lastname: Pritchett
authors.forename: Kumudha
authors.initials: K
authors.lastname: Ramasubbu
authors.forename: Xander H T
authors.initials: XH
authors.lastname: Wehrens
authors.forename: Anita
authors.initials: A
authors.lastname: Deswal
authors.forename: Biykem
authors.initials: B
authors.lastname: Bozkurt
mesh_terms: D000368:Aged; D001794:Blood Pressure; D016208:Databases, Factual; D005260:Female; D006333:Heart Failure / Q000453:epidemiology / Q000401:mortality* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013318:Stroke Volume; D016019:Survival Analysis; D013599:Systole / Q000502:physiology; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000453:epidemiology*